Abstract

Aim

The aromatase inhibitor (AI) Letrozole (L), compared with Tamoxifen (T), improved disease-free survival (DFS) among postmenopausal women with receptor-positive, early breast cancer. The safety profile of the treatments differs markedly, especially in the incidence of musculoskeletal, gynecological and vaso-active symptoms, and type of cardiovascular events (CVD). AIs may increase the risk of specific CVD, perhaps by abnormally high concentrations of aldosterone due to estrogen deficiency. Hypertension (H) in combination with other risk factors (smoking, obesity, diabetes, and hypercholesterolemia) may be the cause of increased CVD in the L arms of BIG1-98.

Methods

BIG 1-98 adverse event data for new or worsening hypertension (NWH) during protocol treatment were analysed retrospectively for 7963 women who received at least one dose of study therapy. H and CVD information were extracted from the CRF based on check boxes and write-ins. NWH was defined as an increase of at least one point in grade of H from baseline (according to CTC 2.0) The proportions of patients with NWH were compared by treatment using chi-squared tests. The relationship between time to develop NWH and treatment (T, L, T-L, L-T); baseline comorbidities; concomitant cardiovascular risk factors, such as hypercholesterolemia, smoking, and pre-existing H; and pre-existing CVD were explored using multivariable Cox PH regression.

Results

All patients had completed or stopped protocol therapy at the time of the analysis. Pre-existing H was reported in 32% of patients. In 440 patients reporting NWH, there were 346 new cases and 94 cases worsening from baseline. Rates of grade 3 or 4 NWH were comparable across all treatments; however, rates of grade 1 or 2 were highest in women receiving L or T alone. Adjusting for pre-existing H, Cox PH models show NWH is related to age and BMI, but not AI treatment.

Conclusions

New or worsening hypertension in postmenopausal women with early breast cancer does not appear to be related to AI treatment, but to age, BMI, and pre-existing hypertension.